Palatal myoclonus responding to lamotrigine.
Palatal myoclonus (PM) is a rare neurological condition with no established treatment. We report on a case of PM with a good response to lamotrigine.
Adult↗
Biomedical subjects
N Brown
Publications and source records attributed to N Brown.
Identification of the Xenopus laevis cDNA for EXT1: a phylogenetic perspective.
The EXT family of genes is involved in the developmentally important biosynthesis of heparan sulfate molecules. Members of the EXT family have a demonstrated role in gastrulation, wing formation in flies, and proper bone development in vertebrates. EXT family members have been isolated from several phylogenetically diverse species. We report here, the isolation of the first Xenopus laevis EXT1 family member and discuss the evolutionary origins of this gene family.
Amino Acid Sequence↗
Baboon CYP11B1: the localization and catalytic activity in baboon adrenal tissue.
A third gene encoding baboon CYP11B1 was isolated and was shown to catalyze only the metabolism of deoxycorticosterone (DOC) to corticosterone. The investigation into the localization of CYP11B1 in the baboon adrenal tissue, using in situ hybridization, showed that mRNA transcripts were predominantly present in the zona reticularis (ZR) and zona fasciculata (ZF). Signal was also observed in the zona glomerulosa (ZG) and scattered within the medulla. Immunohistochemical studies, using rabbit anti-sheep CYP11B1 IgG, indicated that CYP11B1 was expressed only in the zona fasciculata, zona reticularis and in the medulla. CYP11B1 was not detected in the zona glomerulosa. Subsequent Western Blot investigations into the presence of CYP11B1 in baboon adrenal cortex and medullary homogenates indicated CYP11B1 as a single band in the cortex and as two distinct bands in the medulla. CYP11A was present only in the baboon adrenal cortex. The metabolism of deoxycorticosterone and corticosterone was subsequently investigated in the baboon adrenal cortex and medulla. In cortex homogenates, deoxycorticosterone was converted to corticosterone, and neither 18-hydroxycorticosterone nor aldosterone was detected. In medulla homogenates, however, corticosterone was metabolized to aldosterone, as confirmed by APcI-MS.
Adrenal Glands↗
Dose regimen for vancomycin not needing serum peak levels?
AIM: To determine the safety, efficacy, and need to measure peak serum vancomycin concentrations in a neonatal population using a standard vancomycin dosage regimen. METHOD: A total of 101 infants who were admitted to a regional neonatal intensive care unit and received vancomycin (15 mg/kg every 12 or 18 hours depending on postnatal age) were studied retrospectively. Infants who had been started on vancomycin before they were transferred to the unit were excluded. The proportion of infants was measured whose serum vancomycin concentrations were within a conservative therapeutic range of trough 5-10 mg/l, peak 20-40 mg/l, and a less conservative, but still safe, range of trough 5-12 mg/l, peak 15-60 mg/l. RESULTS: Trough concentrations of 5-10 mg/l were achieved by 46.5% of infants, and 5-12 mg/l by 55.4%. Peak concentrations of 20-40 mg/l were found in 83.2% of infants, and 15-60 mg/l in 99.0%. Highest peak concentration was 47.2 mg/l. Some 89.4% of infants with trough concentrations of 5-10 mg/l had a peak concentration of 20-40 mg/l. CONCLUSIONS: The vancomycin dosage regimen used in this study produces acceptable therapeutic serum vancomycin concentrations. Peak serum vancomycin concentrations do not need to be measured in neonates using this dosage regimen.
Anti-Bacterial Agents↗
A protective and agonistic function of IL-12p40 in mycobacterial infection.
IL-12p35(-/-)p40(-/-) mice are highly susceptible to Mycobacterium bovis bacillus Calmette-Guérin (BCG) or Mycobacterium tuberculosis infection. In this study IL-12p35(-/-) mice, which are able to produce endogenous IL-12p40, cleared M. bovis BCG and showed reduced susceptibility to pulmonary M. tuberculosis infection, which was in striking contrast to the outcome of mycobacterial infection in IL-12p35(-/-)p40(-/-) mice. Resistance in wild-type and IL-12p35(-/-) mice was accompanied by protective granuloma formation and Ag-specific delayed-type hypersensitivity responses, which were impaired in susceptible IL-12p35(-/- )p40(-/-) mice. Furthermore, IL-12p35(-/-) mice, but not IL-12p35(-/-)p40(-/-) mice, mounted Ag-specific Th1 and cytotoxic T cell responses. In vivo therapy with rIL-12p40 homodimer restored the impaired delayed-type hypersensitivity responses in M. bovis BCG-infected IL-12p35(-/-)p40(-/-) mice and reverted them to a more resistant phenotype. Together, these results show evidence for a protective and agonistic role of endogenous and exogenous IL-12p40 in mycobacterial infection, which is independent of IL-12p70.
Animals↗
Parks and factors in their success.
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Community Participation↗
Pathology associated with an aquareovirus in captive juvenile Atlantic halibut Hippoglossus hippoglossus and an experimental treatment strategy for a concurrent bacterial infection.
A large-scale mortality of larval and juvenile halibut Hippoglossus hippoglossus occurred at a semi-commercial halibut farm in Atlantic Canada. Investigation of the cause revealed aquareovirus particles in necrotic liver tissue of affected fish. Cytopathic effect on CHSE-214 cell lines occurred from all fish cultured for viruses, and the viral morphology of the particles in culture was consistent with that observed in necrotic host tissue. The virus was placed in the family of Reoviridae, genus Aquareovirus based on morphology and RT-PCR results. Multifocal hepatocellular necrosis was a consistent finding in all fish as well as acute necrosis of proximal renal tubules. Concurrent bacterial infections were present in some specimens. Fish experimentally treated with oxytetracycline or a combination of oxytetracycline and chloramine-T had a significantly lower mortality rate than untreated fish. Fish treated with chloramine-T alone had a significantly elevated mortality rate compared to controls. Despite supportive medical therapy, mortality levels in treated and untreated groups remained elevated, supporting the hypothesis that the primary pathogen was of viral origin. This is the first report of elevated mortalities in Atlantic halibut associated with an aquareovirus.
Animals↗
An integrated physical map of 8q22-q24: use in positional cloning and deletion analysis of Langer-Giedion syndrome.
We have developed an integrated map for a 35-cM area of human chromosome 8 surrounding the Langer-Giedion syndrome deletion region. This map spans from approximately 8q22 to 8q24 and includes 10 hybrid cell intervals, 89 polymorphic STSs, 118 ESTs, and 37 known genes or inferred gene homologies. The map locations of 25 genes including osteoprotegerin, syndecan-2, and autotaxin have been refined from the general locations previously reported. In addition, the map has been used to indicate the location of nine deletions in patients with Langer-Giedion syndrome and trichorhinophalangeal syndrome type I to demonstrate the potential usefulness of the map in the analysis of these complex syndromes. The map will also be of interest to anyone trying to clone positionally disease genes in this region, such as Cohen syndrome (8q22-q23), Klip-Feil syndrome (8q22.2), hereditary spastic paraplegia (8q24), and benign adult familial myoclonic epilepsy (8q23.3-q24.1).
Child↗
The eyeless mouse mutation (ey1) removes an alternative start codon from the Rx/rax homeobox gene.
The eyeless inbred mouse strain ZRDCT has long served as a spontaneous model for human anophthalmia and the evolutionary reduction of eyes that has occurred in some naturally blind mammals. ZRDCT mice have orbits but lack eyes and optic tracts and have hypothalamic abnormalities. Segregation data suggest that a small number of interacting genes are responsible, including at least one major recessive locus, ey1. Although predicted since the 1940s, these loci were never identified. We mapped ey1 to chromosome 18 using an F2 genome scan and there found a Met10-->Leu mutation in Rx/rax, a homeobox gene that is expressed in the anterior headfold, developing retina, pineal, and hypothalamus and is translated via a leaky scanning mechanism. The mutation affects a conserved AUG codon that functions as an alternative translation initiation site and consequently reduces the abundance of Rx protein. In contrast to a targeted Rx null allele, which causes anophthalmia, central nervous system defects, and neonatal death, the hypomorphic M10L allele is fully viable.
Alternative Splicing↗
Comparative analysis of reproductive cycles in female Persian gazelle (Gazella subgutturosa subgutturosa) (Central Asia) and sand gazelle (Gazella subgutturosa marica) (Arabian Peninsula).
This study was conducted at the Bukhara breeding centre (Ouzbekistan, Central Asia) on Persian gazelles (Gazella subgutturosa subgutturosa) and at Thumammah (Saudi Arabia) on sand gazelles (Gazella subgutturosa marica). Plasma prolactin (PRL) and progesterone were determined in groups of females. Because these females were under two different photoperiods (20 degrees N in Saudi Arabia and 40 degrees N in Uzbekistan), some Persian females were treated with melatonin implants. Both groups of females living in natural environment in Uzbekistan and in Saudi Arabia exhibited an estrus (autumn and early winter) and an anestrus season (spring and summer). Both groups of females exhibited estrous and anestrous seasons. The estrous season was shorter in females from Uzbekistan. During the anestrous season, progesterone concentrations remained at basal levels in Persian gazelles (Uzbekistan) while in sand gazelles (Saudi Arabia) hormonal concentrations were higher than in Persian gazelles until August and decreased to similar concentrations in September-October. Moreover, the pattern of PRL significantly differed in the two groups. Persian gazelles exhibited a clear seasonal pattern with significantly high levels of PRL in June whereas in the sand gazelle PRL did not rise significantly in summer and fluctuated widely. Melatonin treatment significantly depressed PRL concentrations but did not affect the length of the estrous season in Persian gazelles, suggesting that the reproductive cycle was entrained by an endogenous rhythm.
Anestrus↗
The functional and structural outcome of inner ear gene transfer via the vestibular and cochlear fluids in mice.
Mice present an ideal model for inner ear gene therapy because their genome is being rapidly sequenced, their generation time is relatively short, and they serve as a valuable model for human hereditary inner ear disease. However, the small size of the mouse inner ear poses a particular challenge for surgical procedures. We have developed a new approach for viral inoculation into the mature mouse inner ear, using a replication-deficient adenovirus expressing the bacterial gene lacZ. We administered the virus through the posterior semicircular canal (canalostomy) and into the cochlea (cochleostomy). Both approaches caused lacZ to be expressed in cells lining the perilymphatic space. One canalostomy case showed gene expression in sensory cells of the crista ampullaris, whereas the cochleostomy group showed gene expression in the sensory cells in the organ of Corti and saccule. Functional tests after the surgery showed that the canalostomy preserved hearing, whereas the cochleostomy did not. Any vestibular function transiently lost after the canalostomy was recovered. Our findings indicate that inoculation of adenovirus vectors into the mouse inner ear through the semicircular canal has the potential to efficiently introduce transgenes to the vestibular system and the cochlea without compromising hearing.
Adenoviridae↗
Transgenics, uncertainty and public credibility.
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Animals↗
IL-1beta and IL-8 in human fetal membranes: changes with gestational age, labor, and culture conditions.
PROBLEM: Interleukin (IL)-1beta and IL-8 are associated with labor. This study aimed to characterize their concentrations in fetal membranes and any changes in these with advancing gestation and to define as to whether there are interactions between the membranes in their expression. METHOD OF STUDY: mRNA and protein content of amnion and choriodecidua at increasing gestations and before and after labor at term were quantified. Membranes were also collected before and after labor, separated, and cultured. Protein production was measured by ELISA. RESULTS: IL-1beta and IL-8 concentration increased in third trimester amnion and choriodecidua. Further increased expression of mRNA of both cytokines was found after labor in both membranes except IL-8 production by amnion. Choriodecidua produced more of each cytokine than amnion, however, no interaction between the membranes was demonstrated by culture. CONCLUSIONS: Increasing expression of IL-1beta and IL-8 in amnion and choriodecidua in the third trimester and after labor supports a role for these cytokines in the establishment of labor.
Amnion↗
Assembly of microarrays for genome-wide measurement of DNA copy number.
We have assembled arrays of approximately 2,400 BAC clones for measurement of DNA copy number across the human genome. The arrays provide precise measurement (s.d. of log2 ratios=0.05-0.10) in cell lines and clinical material, so that we can reliably detect and quantify high-level amplifications and single-copy alterations in diploid, polyploid and heterogeneous backgrounds.
Aneuploidy↗
A multicenter United States-Canadian trial to assess lamivudine monotherapy before and after liver transplantation for chronic hepatitis B.
Seventy-seven liver transplant candidates were enrolled in a multicenter study in which patients were treated with lamivudine (100 mg daily) without the adjunctive use of hepatitis B immune globulin. Treatment was begun while patients awaited liver transplantation and continued after transplantation. All were hepatitis B surface antigen (HBsAg) positive, and 61% had detectable hepatitis B e antigen (HBeAg) and HBV DNA when treatment was begun. Forty-seven underwent liver transplantation and 30 did not. Median study participation was 38 months (range, 2.7-48.5) in the transplanted patients and 26 months (range, 0.1-37) in the nontransplanted group. Twenty-five of 42 (60%) transplanted patients with 12 or more weeks of posttransplantation follow-up were HBsAg negative at the last study visit. At treatment week 156, 13 of 22 (59%) remained HBsAg negative, and all 9 reinfected patients were HBV-DNA positive before treatment. In the nontransplanted patients, HBeAg was initially detectable in 20 of 27 (74%) but this decreased to 3 of 17 (18%) after 104 weeks of treatment, and significant improvement in biochemical parameters was observed. HBV-DNA polymerase mutants were detected in 15 (21%) and 6 (20%) of the transplanted and nontransplanted patients, respectively. When compared with historical cohorts, lamivudine-treated patients appeared to have improved survival, and transplanted patients had a decrease in the rate of recurrent HBV infection. Lamivudine therapy was partially effective in preventing recurrent HBV infection when given before and after transplantation. Thus, future trials using a combination of HBIg and lamivudine are needed to assess the optimal prophylactic therapy.
Adult↗
A multicenter study of lamivudine treatment in 33 patients with hepatitis B after liver transplantation.
Hepatitis B virus (HBV) infection after liver transplantation (LT) may lead to severe and rapidly progressive graft failure. Antiviral treatment may be of benefit in selected patients with recurrent hepatitis B post-LT. The aim of this prospective open-label study is to determine the safety and efficacy of lamivudine in 33 liver transplant recipients with active HBV infection. The median time from LT to study enrollment was 51 months, all patients were hepatitis B surface antigen positive, and 75% and 94% of subjects had detectable hepatitis B e antigen (HBeAg) and HBV DNA at entry, respectively. The median duration of lamivudine treatment on study was 85 weeks, during which time median HBV DNA levels became undetectable by 16 weeks and 9% of patients lost previously detectable HBeAg. Serum alanine aminotransferase (ALT) levels improved in most patients and normalized in 27% of patients with elevated values pretreatment. Serum bilirubin and albumin levels significantly improved in patients with abnormal values at entry (P <.05). Virological breakthrough was detected in 13 subjects after a median of 61 weeks of lamivudine treatment and was confirmed to be caused by YMDD mutants in all patients tested. None of the patients with virological breakthrough showed a complete loss of clinical response to lamivudine. Serum ALT and bilirubin levels in patients with and without virological breakthrough were not significantly different at last study follow-up. Study results show that lamivudine is safe and effective in liver transplant recipients with recurrent hepatitis B. However, the high rate of virological breakthrough with prolonged therapy indicates the need for further studies of combination antiviral therapy in this patient population. Our results and others further establish the improving long-term outcomes with LT for patients with hepatitis B through advances in prevention of reinfection, as well as the availability of safe and effective antiviral therapies to treat patients with HBV recurrence.
Adult↗
Isolated digital infarction associated with anticentromere antibody.
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Aged↗
Switching between science and culture in transpecies transplantation.
This article discusses xenotransplantation (XTP: the surgical role of nonhuman tissues, organs, and cells for human transplantation) and examines the way its scientific promoters have defended their technology against potentially damaging public representations. The authors explore the criteria used to legitimate the selection of the pig as the best species from which to "harvest" transplant tissues in the future. The authors' analysis shows that scientists and medical practitioners routinely switch between scientific and cultural repertoires. These repertoires enable such actors to exchange expert identities in scientific discourse for public identities in cultural discourse. These discourses map onto similarities and differences between animal donors and human hosts. Finally, the case is used to comment on a number of related approaches where the dynamics of medical and scientific authority are discussed.
Animal Rights↗